Dr Lisa Mielke announced among Victoria's most outstanding mid-career cancer researchers

Dr Lisa Mielke announced among Victoria's most outstanding mid-career cancer researchers.

The Olivia Newton-John Cancer Research Institute is thrilled to announce that Dr. Lisa Mielke has been honoured with the prestigious 2023-2024 Monash Partners Comprehensive Cancer Consortium (MPCCC) Mid-Career Award for Outstanding Cancer Research. This accolade is a testament to Dr. Mielke’s outstanding contributions to cancer research, particularly her work in cancer immunology, which focuses on enhancing the anti-tumour response of a relatively understudied immune cell type in the fight against bowel cancer.

Dr. Mielke leads the Mucosal Immunity and Cancer Laboratory at ONJCRI, where her research delves into the intricate relationship between immune cells and cancer, with a particular focus on bowel cancer. Her work has unveiled the critical role of gamma delta (γδ) T cells in preventing the development and progression of cancer within the large bowel. Dr. Mielke and her team discovered that a molecule called TCF-1, suppresses the natural activity of γδ T cells, which are crucial for combating bowel cancer. In pre-clinical studies they could show that when TCF-1 was deleted in these immune cells, the anti-tumour immunity significantly increased, resulting in a reduction in tumour burden.

This insight may open new avenues for improving immunotherapy treatments for bowel cancer, by targeting TCF-1, thereby enhancing the anti-tumour response. The significance of Dr. Mielke’s research extends beyond the scientific community.

By focusing on anticancer therapies that aim to minimise treatment toxicity, her work aligns with ONJCRI’s mission to improve quality of life for cancer patients. Her achievements exemplify the institute’s commitment to pioneering research that offers hope for more effective cancer treatments. Chief Executive Officer of ONJCRI, Professor Marco Herold, stated “there is no doubt, Lisa is destined to be a world leader in the field of cancer immunology.  Her collaborative approach to research, enthusiasm, and talent to teach the next generation of scientists will lead to many exciting discoveries benefitting cancer patients. We are immensely proud of Lisa, and we look forward to seeing the impact of her work in the future.”

By supporting research like Dr. Mielke’s, we can all contribute to the fight against cancer, entering a new era of more effective and compassionate care.


Research Assistant

Outsmart Cancer with Us!

Join Our Dynamic Research Team!

Make a real difference in the fight against cancer.

The Olivia Newton-John Cancer Research Institute (ONJCRI) is searching for a passionate and skilled Research Assistant to join our vibrant team. You’ll have the opportunity to work alongside leading local, national, and international researchers and clinicians, contributing to groundbreaking cancer treatments that improve lives.

Here’s why you’ll love this role:

  • Be part of something bigger: Contribute to cutting-edge research aimed at defeating cancer.
  • Work in a collaborative environment: Learn and grow alongside a supportive and diverse team.
  • Shape your schedule: Enjoy a hybrid, flexible work model that fits your needs.
  • Boost your career: Gain valuable experience and access generous professional development opportunities.
  • Receive excellent benefits: Enjoy a competitive salary with salary packaging up to $18,550 and 5 extra paid Institute Days off per year.

What you’ll do:

  • Perform critical research experiments, supporting various lab projects.
  • Assist with day-to-day lab operations to ensure smooth functioning.
  • Analyze data, prepare reports, and contribute to publications.
  • Maintain essential lab protocols and databases.
  • And much more!

We’re looking for someone with:

  • A Bachelor of Science (Honours) and 3+ years of research assistant experience.
  • Experience in processing human samples, running antibody panels, and cell culture.
  • Strong analytical and organizational skills.
  • A passion for research and a dedication to making a difference.

Ready to join the fight against cancer?

Apply now and take the next step in your rewarding career!

We can’t wait to hear from you!

Please forward your completed application, quoting reference number ONJCRI-110/2024 to Andreas Behren, Tumour Immunology Laboratory Head, at jobs@onjcri.org.au, with the following information:

  • Your cover letter, stating why you would be a good fit for the role;
  • Your CV;
  • 3 referee details (referees will only be contacted after interview.)

Don’t forget to mention:

  • Why you’re passionate about cancer research.
  • What makes you a great fit for our team.
  • How you can contribute to our mission.

The Institute is committed to creating a diverse and inclusive work environment and workforce and we strongly encourage people from all backgrounds to apply.


BioNTech Founders visit the Olivia Newton-John Cancer Research Institute

BioNTech Founders visit the Olivia Newton-John Cancer Research Institute, marking new innovative possibilities for combatting cancer.

La Trobe University was recently announced as the new home for the manufacturing of investigational mRNA therapies, for the global biotechnology company BioNTech, in a multi-year strategic partnership with the Victorian State Government. The facility, to be located at La Trobe University’s Bundoora campus, is based on the Company’s high-tech, digitally enabled modular manufacturing units, the BioNTainers.

The facility will not only produce mRNA therapies but also drive research into mRNA-based vaccine and therapy development, with a focus on addressing cancers with high unmet clinical need. BioNTech, renowned for its ground-breaking work alongside its partner, Pfizer in creating the world’s first approved COVID-19 vaccine, Comirnaty® (BNT162b2), stands as a global leader in next generation immunotherapy. The company is at the forefront of pioneering novel therapies for cancer, and other serious diseases.

In a significant event held in October 2023, BioNTech co-founders Professor Uğur Şahin, Chief Executive Officer, and Professor Özlem Türeci, Chief Medical Officer, visited the Olivia Newton-John Cancer Research Institute, La Trobe University’s School of Cancer Medicine. The visit preceded a special ceremony in Melbourne, where Professors Şahin and Türeci, together with Professor Sharon Lewin AO (Director, Doherty Institute) were presented with an Honorary Doctor of Science by La Trobe University Chancellor, the Hon John Brumby AO, who is also the past inaugural Chair of the ONJCRI.

Accompanied by their team, the BioNTech founders were joined by members of La Trobe University’s Senior Executive Group and staff, as well as representatives from mRNA Victoria, the ONJCRI Board of Directors and Austin Health.

The day commenced with an insightful tour of the ONJCRI facilities, guided by Institute staff and students, and concluded with a presentation by Professor Marco Herold, Chief Executive Officer of the Olivia Newton-John Cancer Research Institute and Head of the La Trobe University School of Cancer Medicine.

Expressing enthusiasm about the partnership, Professor Herold said;

“We are excited by this strategic partnership between BioNTech and La Trobe University to explore mRNA technology innovations for the treatment of currently incurable cancers. As an Institute with key strengths in immunotherapy, we are eager to embark on collaborative projects with BioNTech to harness the power of mRNA technology for effective cancer treatment”.

Image source: La Trobe University


Discovering new approaches to prevent metastasis of breast, colon and liver cancers

Discovering new approaches to prevent metastasis of breast, colon and liver cancers

Supervisors: Dr Bhupinder Pal, Prof John Mariadason and A/Prof Naiyang Fu (WEHI)

Laboratories: Cancer Single Cell Genomics Laboratory

Colorectal cancer claims the lives of over 5000 Australian’s each year.  Chemotherapy and radiation therapy are routinely used to treat these tumours, however not all patients respond to these treatments. This PhD project will seek to develop new ways to increase the effectiveness of chemotherapy and radiation therapy by testing new therapeutics in cell line, organoid and mouse models of this disease, and investigating their underlying mechanisms of action. It also involves the use of genetic screens such as CRISPR/Cas9 to discover new drivers of drug resistance.

The project will provide the candidate with extensive knowledge of cancer biology, and the transcriptional and signaling pathways which drive the response to drug treatment. The candidate will also gain expertise into the use of cutting-edge discovery tools such as molecular profiling, CRISPR screening and drug screening, and the use of mouse models and clinical samples to address critical questions that can improve outcomes for cancer patients.


Enhancing the efficacy of chemotherapy and radiation therapy in colorectal cancer

Enhancing the efficacy of chemotherapy and radiation therapy in colorectal cancer.

Supervisors: Prof John Mariadason, Dr Ian Luk, Dr Fiona Chionh

Laboratories: Oncogenic Transcription Laboratory

Colorectal cancer claims the lives of over 5000 Australian’s each year.  Chemotherapy and radiation therapy are routinely used to treat these tumours, however not all patients respond to these treatments. This PhD project will seek to develop new ways to increase the effectiveness of chemotherapy and radiation therapy by testing new therapeutics in cell line, organoid and mouse models of this disease, and investigating their underlying mechanisms of action. It also involves the use of genetic screens such as CRISPR/Cas9 to discover new drivers of drug resistance.

The project will provide the candidate with extensive knowledge of cancer biology, and the transcriptional and signaling pathways which drive the response to drug treatment. The candidate will also gain expertise into the use of cutting-edge discovery tools such as molecular profiling, CRISPR screening and drug screening, and the use of mouse models and clinical samples to address critical questions that can improve outcomes for cancer patients.


Tuft Cells in the GI Cancer Microbiome: Unraveling their Role in Microbial Regulation

Tuft Cells in the GI Cancer Microbiome: Unraveling their Role in Microbial Regulation

Supervisors: A/Prof Michael Buchert, Prof Matthias Ernst

Laboratories: Cancer and Inflammation Laboratory

Until recently, it was common to think that tumours are simply masses of a patient’s own cells that malfunction and grow uncontrollably when they, in fact, are communities of many different cell types. New research has now shown that tumours also play hosts to a collection of other life-forms entirely – microorganisms such as bacteria and fungi, some of which thrive in the environment around the tumour while others live inside the tumour cells themselves. Until recently it was unknown what roles these microbes play in tumours, however novel findings show that they can either assist or oppose tumour development and progression. For example, bacteria can protect the tumours by inactivating chemotherapy drugs or altering the ability of the immune system to target and destroy tumour cells, while other bacteria protect the body from tumour growth by detoxifying carcinogens or reducing levels of harmful reactive oxygen molecules that can damage DNA. This area of cancer microbiology is an emerging and exciting topic of research and promises to lead to new approaches for treating and preventing cancers.

Tuft cells (TCs) are a rare chemosensory epithelial cell type in the gastrointestinal (GI) tract and sole source of epithelial interleukin (IL) 25. TCs have an important function as immune sentinels in the epithelium that relay danger signals to the mucosa-resident immune cells in order to maintain a healthy tissue. Recently, TCs were shown to detect the presence of certain microbial metabolites and to induce the expression of IL13 in cells of the innate immune system which in turn altered the expression profile of antimicrobial peptides (AMPs) in epithelial cell types such as Paneth and goblet cells which led to changes in the composition of the mucosal microbiota. Moreover, treatment of mice with IL25 alone was sufficient to induce similar changes to the microbiota in the absence of microbial metabolites. Thus, TCs can sense and regulate the makeup of the resident microbial communities.

The aim of this PhD project is to investigate whether TCs inside or outside of the tumour tissue are involved in the regulation of the tumour-associated microbiota. We will use preclinical GI tumour models where we can specifically ablate TCs either in the tumour or in the unaffected surrounding healthy tissue and determine the abundance and composition of microbial communities by 16S RNA sequencing.  We will further complement these experiments by pharmacologically blocking the activity of IL25 and IL13 in vivo. Lastly, we will determine the impact of both genetic and pharmacologic approaches on the ability of the host immune system or chemotherapy treatments to limit tumour growth.

The project will provide the candidate with the opportunity to work in cancer microbiology, an emergent and exciting new area of cancer research. Basic training in immunology/microbiology or cancer biology (Honours or Masters minimum) will be required.

Techniques involved:

  • Flow cytometry
  • Immunofluorescent microscopy
  • 16S RNA sequencing

Recommended reading:

  1. The microbiome and human cancer. Science. 2021 Mar 26;371(6536)
  2. Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape. Proc Natl Acad Sci U S A. 2023 Jun 6;120(23)
  3. Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa. Proc Natl Acad Sci U S A. 2023 Jun 20;120(25)


Choosing the right T cell for CAR therapy approaches

Choosing the right T cell for CAR therapy approaches

Supervisors: A/Prof Andreas Behren, A/Prof Paul Beavis (PMCC), Dr Fern Koay (PDI)

Laboratories: Tumour Immunology Laboratory

Chimeric Antigen Receptor (CAR) T cells have shown clinical success in hematological cancers with multiple therapies approved around the world. However, no similar success can be reported for the treatment of human solid tumours. Multiple strategies have been suggested to overcome the issues related to treatment failure in this setting including poor T cell infiltration and a suppressive tumour microenvironment (TME) affecting CAR T cell efficacy.

T cell subset heterogeneity has been characterized in depth over the last decade, however direct head-to-head comparisons between vastly distinct classes of T cells and their utility for CAR T cell approaches have not been performed. Critically, beyond CD4 and CD8 classical T cells, non-conventional T cell subsets such as MAIT and gd T cells have higher organ-homing capacity and migrate preferentially to nonlymphoid tissue, where they can react rapidly to stimulus. Here, we hypothesise that MAIT cells and gd T cells may have several advantages over conventional T cells including their potential to be utilized in a third-party manner when generated from healthy donors and their increased cytotoxic capacity relative to conventional CD4 and CD8 T cells. Thus, we aim to holistically explore these T cell subsets and their propensity to act as CAR T cell therapeutics in the setting of solid tumours.

For this we will generate CD4, CD8, MAIT and gd T cell subsets expressing CARs of the same specificity and test their ability in parallel for in vitro cytotoxicity and cytokine secretion against tumour cells utilizing 2D and 3D cell culture models .We will identify the best layout of CAR constructs for armoured CAR approaches (activation domains and cytokine secretion) for the various T cell subsets and compare their in vivo ability to infiltrate and target solid tumours in mouse models. Within in vivo experiments, we will also exploit the amenability of unconventional CAR T cells as they can be selectively activated and expanded with TCR agonists such as antigens to enhance cell numbers or overall therapy persistence. In addition, we will utilize CRISPR-Cas9 technology to specifically override candidate molecules contributing to the immune-suppressive state of our generated CAR T cells (e.g. PD-1KO T cells) via approaches that have already been optimized within the host laboratories (Ref Giuffrida et al. 2021, Nature Communications).

The project will take place across 3 of Melbourne’s leading cancer and immunology institutes (PeterMac/PDI/ONJCRI) with lab rotations amongst these, leveraging the developed methodologies and expertise in these laboratories in unconventional T cell biology, cancer immunology, and CAR T cell development.


Improving response to immunotherapy

Improving response to immunotherapy

Supervisors:  A/Prof Doug Fairlie, Dr Conor Kearney, Erinna Lee

Laboratories: Molecular Immunology Laboratory, Cell Death and Survival Laboratory

Immunotherapy has reshaped the way we treat cancer. However, obstacles still exist including the inability to predict treatment efficacy, patient response and the development of resistance. Utilising the expertise of our joint labs in cancer immunology (Kearney) and membrane trafficking pathways (Lee/Fairlie), this PhD project will employ targeted CRISPR-based screening technologies to identify mechanisms that sensitise or inhibit tumour cells to T cell-mediated killing. For this project, the PhD candidate will utilise and develop skills in advanced molecular biology (in particular CRISPR screens), cell biology, membrane trafficking and cancer immunology.


CRISPR Down Under Symposium 2023

Registrations are now open for the inaugural CRISPR Down Under Symposium

 

This event will link CRISPR researchers across Australia, providing a multidisciplinary forum to discuss emerging CRISPR technologies and their application in advancing medical research.

This one-day meeting will be held in person format on Friday October 27th at the Olivia Newton-John Cancer Research Institute (Heidelberg, VIC). All current and aspiring genome engineers are encouraged to register to hear the latest achievements in all aspects of basic and translational CRISPR biology. 

Registration and abstract submission is open from now until Friday September 15th, at crispr.org.au/registration. Please note that registration places are limited and preference will be given to registrants submitting an abstract.

Confirmed speakers:

  • Two international speakers: Dana Foss (San Fransisco, USA) & Ben Haley (Montreal, Canada)
  • Two national speakers: Pilar Blancafort (Harry Perkins/UCSF, WA) & Paul Thomas (SAHMRI, SA)
  • Four local Victorian speakers: Marco Herold (ONJCRI, CEO), Mohamed Fareh (Peter Mac), Sarah Diepstraten (WEHI), Gavin Knott (Monash BDI).

The 2023 CRISPR Down Under organising committee:

  • Carolyn Shembrey
  • Emily Lelliott
  • Christina Koenig

Generously supported by:


Olivia Newton-John Cancer Research Institute leads $4M project creating Australia’s first advanced lung cancer biobank to transform research and improve treatments for patients

Multimillion-dollar ‘TRACKER’ research project received funding boost from Australian Government this week to collect and analyse patient samples helping to address unmet clinical need for lung cancer patients

The Olivia Newton-John Cancer Research Institute, the La Trobe University School of Cancer Medicine, has received multimillion-dollar funding to establish Australia’s first longitudinal biobank for advanced lung cancer, including $3 million funding from the Australian Government’s Medical Research Futures Fund and $1 million in kind support from project partners and supporters around Australia.

Lung cancer is the leading cause of cancer death in Australia, and advanced lung cancer is an area of unmet clinical need as 80% of patients present with inoperable metastatic disease. One of the greatest challenges in metastatic lung cancer is resistance to treatment, hence there is an urgent need to identify biomarkers to guide improved treatments for patients.

A first-of-its-kind in Australia, the Tissue Repository of Airway Cancers for Knowledge Expansion of Resistance (TRACKER) national project involves the longitudinal collection of tissue and blood samples from patients diagnosed with advanced lung cancer across their cancer journey to create a biobank that will help researchers to identify drivers of resistance to immunotherapy.

The TRACKER research project is led by Olivia Newton-John Cancer Research Institute / La Trobe University School of Cancer Medicine and was conceived and developed in a collaborative effort from clinician-scientists at Austin Health (Dr Tracy Leong and Dr Sagun Parakh), researchers at the ONJCRI (Associate Professor Andreas Behren, Head of the Tumour Immunology Laboratory, and Postdoctoral Research Fellow Dr Ashleigh Poh), the Peter MacCallum Cancer Centre (Dr Stephen Wong), the Walter and Eliza Hall Institute (WEHI) and people with lived experience of lung cancer.

Project lead, Associate Professor Andreas Behren from the Olivia Newton-John Cancer Research Institute, explained: “Our advanced lung cancer TRACKER biobank will allow researchers to track the progression of the disease at the molecular level, with the aim of understanding why current therapies are failing so many patients and suggesting new approaches.”

“Currently, without TRACKER, this research is not possible because there is a lack of sufficient samples and a lack of easily accessible technology for in-depth interrogation of small tissue specimens,” said A/Prof Behren.

TRACKER Project lead, A/Prof Andreas Behren

Most important for patients – TRACKER was co-designed by consumers with lived experience to ensure that it would be non-surgical and minimally invasive, from initial diagnosis and throughout their treatment, including cutting-edge techniques to obtain endobronchial ultrasound tumour samples, liquid biopsies, and bronchoalveolar lavage fluid.

As a consumer advocate with lived experience of lung cancer, Lisa Briggs, was instrumental in co-designing the sampling collection process and building the TRACKER consumer team who partnered with researchers and clinicians. She explained how the care of cancer patients is at the forefront of her mind and how crucial the TRACKER project will be for improving outcomes for lung cancer patients.

“Our tumour samples are precious to us – they contain valuable information to unlock answers about our care. Knowing they will be safely collected, stored, and utilised to help advance lung cancer research with minimal waste, gives me total satisfaction and fills me with hope. Hope that these answers will someday be found, but also hope that our care will be improved. As a wife and mum of 2 young children, everyday matters,” said Lisa Briggs.

“This research is critically important because I understand firsthand the lengths a patient has to go to, in order for a tissue sample to be taken.”

“No longer will we have to worry about silo-ed approaches to research. This National TRACKER biobank not only offers opportunities for collaboration, but also the ability to improve the quality of research by building on the number and type of samples available for use. As a patient this is an exciting prospect, as it enhances the potential for improving outcomes,” said Lisa Briggs.

Clinician-scientists Dr Tracy Leong, Director of Interventional Pulmonology, and Dr Sagun Parakh, Oncologist and Postdoctoral researcher from Austin Health are clinical leads of the TRACKER research project.

“TRACKER will provide a unique dataset that will enable us to transform our clinical approach to metastatic lung cancer and bring us one step closer to improving outcomes for lung cancer patients,” said Dr Leong.

Collection and research sites for TRACKER will include the Austin Hospital (VIC), Royal Melbourne Hospital (VIC), Walter and Eliza Hall Institute (VIC), Macquarie University Hospital (NSW), St Vincent’s Hospital (NSW), The Garvan Institute of Medical Research (NSW), Royal Adelaide Hospital (SA), Fiona Stanley Hospital (WA), Sir Charles Gairdner Hospital (WA), The Prince Charles Hospital (QLD) and the Royal Brisbane and Women’s Hospital (QLD).